In theory, a wide range of sensory and motor dysfunctions can be treated by electrical stimulation to evoke patterns of neural activity similar to those that underlie normal function. In practice, however, such stimulation typically has required relatively expensive and large devices implanted by a surgeon or skin surface stimulation applied by a trained therapist. We have developed a new class of generic devices that can deliver precisely metered stimulation pulses to an arbitrary number of nerve and muscle sites. These leadless BIOnic Neurons (BlONsTM) can be injected through a 12 gauge hypodermic needle into the desired locations. They receive their power and digital command signals by RF telemetry from a single, externally worn transmission coil. They have been used extensively in preclinical animal studies of the effects of electrically induced muscle exercise. A clinical trial for shoulder subluxation began in November, 1999, and a second for osteoarthritis of the knee began in June 2000, both with excellent results to date. Under this BRP, we will design and build BION1 implants and accessory components for testing, programming and controlling them in patients. We will develop and test a range of clinical applications to determine safety and efficacy and to understand further the mechanisms underlying neuromuscular pathology and treatment. In the first five years, these applications include activating and strengthening muscles in the hand, shoulder, and ankle in patients suffering from stroke and cerebral palsy. Enhancements of the current BION1 technology are under development (with separate NIH funding) to improve power efficiency and portability and to incorporate sensing and back-telemetry for functional electrical stimulation (FES). In subsequent years, we will expand the clinical applications to provide more complete rehabilitation of multijoint dysfunctions that commonly occur in these disorders and we will incorporate advanced BION2 technology to provide functional reanimation of paralyzed limbs using neural prosthetic control.